The role of angiogenic factors in the pathogenesis of placenta accreta spectrum in women with placenta previa


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Abstract

Objective: To investigate the contribution of angiogenic factors to the pathogenesis of placenta accreta spectrum (PAS) in women with placenta previa to identify additional biomarkers of abnormal placental invasion. Materials and methods: Baseline evaluation included measurement of serum concentrations of PlGF, VEGF, sFlt-1, Doppler ultrasound in women with placenta previa (n=42) and with PAS (n=46), immunohistochemistry of local expression of VEGFand Flt-1in placenta previa (n=17), pl. accreta (n=16), pl. increta (n=18), pl. percreta (n = 6) groups. Results: Women with PAS had lower expression of Flt-1 in chorionic villi than those without PAS. This was found both in (p=0.02; <0.001; 0.003for pl. accreta, increta, percreta, respectively) and outside of the invasion zone for invasive forms of PAS (p=0.005; 0.003for pl. increta, percreta, respectively). These changes were associated with a decrease in serum sFlt-1/PlGF in PAS (1.65 vs 3.0, p=0.035). The increase in local VEGF expression in PAS was not in parallel with the changes in serum concentrations of this biomarker. Women with PAS were more likely to have increased subplacental vascularization according to color Doppler; a combination of > 3 US signs (91.3% vs 40.5%; 67.4% vs 11.9%, p<0.001<0.001, respectively). There were no differences in uteroplacental hemodynamics between groups according to spectral Doppler (p=0.323). Ultrasound for the diagnosis of PAS demonstrated sensitivity of 95.7%, specificity of 54.8%, positive predictive value of 69.8%, negative predictive value of 92.0%, and accuracy of 76.1%. Conclusion: The decrease in serum sFlt-1/PlGF in pregnant women with PAS in the third trimester is consistent with a decrease in local Flt-1 expression in the chorionic villi and can be used as an additional biomarker of PAS in women with placenta previa. Assessment of multiple ultrasound signs of PAS may improve the specificity and accuracy of antenatal diagnosis in patients at risk.

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About the authors

Tatiana B. Makukhina

Regional Clinical Hospital No. 2, Ministry of Health of the Krasnodar Krai; Kuban State Medical University, Ministry of Health of Russia

Email: soltamna@mah.ru
PhD, Associate Professor, Associate Professor at the Department of Obstetrics, Gynecology and Perinatology; Diagnostic Medical Sonographer

Grigoriy A. Penzhoyan

Regional Clinical Hospital No. 2, Ministry of Health of the Krasnodar Krai; Kuban State Medical University, Ministry of Health of Russia

Email: pga05@mail.ru
Dr. Med. Sci., Professor, Head of the Department of Obstetrics, Gynecology and Perinatology; Obstetrician-Gynecologist

Radmila V. Morozova

Children's Regional Clinical Hospital, Ministry of Health of the Krasnodar Krai

Email: radohka@mail.ru
Head of the Department of Anatomic Pathology

Oksana I. Zadornaya

Children's Regional Clinical Hospital, Ministry of Health of the Krasnodar Krai

Biologist at the Department of Anatomic Pathology

Maria V. Dontsova

Kuban State University, Ministry of Science and Higher Education of Russia

Email: dontsova@yandex.ru
PhD (sociological sciences), Associate Professor, Associate Professor at the Department of Sociology

Natalia V. Krivonosova

Kuban State Medical University, Ministry of Health of Russia

Email: natalja.krivonosova@yandex.ru
PhD, Associate Professor, Associate Professor at the Department of Obstetrics, Gynecology and Perinatology

Arpine M. Amirkhanyan

Regional Clinical Hospital No. 2, Ministry of Health of the Krasnodar Krai; Kuban State Medical University, Ministry of Health of Russia

Email: arm2035@yandex.ru
Associate Professor at the Department of Obstetrics, Gynecology and Perinatology; Obstetrician-Gynecologist

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